Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
Dev Comp Immunol. 2012 Feb;36(2):378-84. doi: 10.1016/j.dci.2011.07.010. Epub 2011 Aug 25.
Virus like particles (VLPs) against viral pathogens not only constitute a novel approach for the development of antiviral vaccines for an specific virus, but also for the creation of multivalent vaccines in which antigens from other pathogens may be expressed on the surface of these VLPs. Despite positive results on protection for many of these VLPs in both fish and mammals, not many studies have focused on the immune response triggered by these particles; studies that may provide hints for the identification of immune mechanisms responsible for antiviral protection, which are mostly unknown in fish. In the current work, we have studied the levels of transcription of several immune genes in the spleen of rainbow trout (Oncorhynchus mykiss) intraperitoneally injected with VLPs from infectious pancreatic necrosis virus (IPNV) focusing on the chemokine response as well as the response of genes related to interferon (IFN) production. Surprisingly, the capacity of VLPs to induce chemokines differed from that of live IPNV, suggesting a direct effect of viral replication on the chemokine response in this organ. While VLPs up-regulated the transcription of CK3, CK10 and CXCd and down-modulated CK5B, CK6 and CK9 transcription, a previous study in which the transcription of γIP, CXCd, CK1, CK3, CK5B, CK6, CK7A, CK9 and CK12 had been studied demonstrated that IPNV only significantly up-regulated CK6 and down-modulated CK3 in the spleen. On the other hand, the administration of VLPs produced a strong mobilization to the peritoneum of CD4(+), IgM(+), IgT(+) and CD83(+) leukocytes similar to that induced by the live viral infection. In both cases, this leukocyte recruitment seemed to be greatly mediated through CK3, CK5B, CK9 and CK10 chemokine production. These results together with the fact that VLPs strongly induced non-specific lymphocyte proliferation and specific anti-IPNV antibody production point to VLPs as excellent candidates for vaccine development.
病毒样颗粒（VLPs）针对病毒病原体不仅构成了开发针对特定病毒的抗病毒疫苗的新方法，而且还构成了在这些 VLPs 表面表达来自其他病原体的抗原的多价疫苗的新方法。尽管这些 VLPs 在鱼类和哺乳动物中都有积极的保护效果，但针对这些颗粒引发的免疫反应的研究并不多；这些研究可能为识别负责抗病毒保护的免疫机制提供线索，而鱼类中的这些机制大多未知。在当前的工作中，我们研究了经传染性胰脏坏死病毒（IPNV）VLPs 腹腔注射的虹鳟鱼（Oncorhynchus mykiss）脾脏中几种免疫基因的转录水平，重点研究趋化因子反应以及与干扰素（IFN）产生相关的基因反应。令人惊讶的是，VLPs 诱导趋化因子的能力与活的 IPNV 不同，这表明病毒复制对该器官中趋化因子反应有直接影响。虽然 VLPs 上调了 CK3、CK10 和 CXCd 的转录，并下调了 CK5B、CK6 和 CK9 的转录，但在之前的研究中，γIP、CXCd、CK1、CK3、CK5B、CK6、CK7A、CK9 和 CK12 的转录研究表明，IPNV 仅在脾脏中显著上调 CK6 并下调 CK3。另一方面，VLPs 的给药引起 CD4(+)、IgM(+)、IgT(+) 和 CD83(+) 白细胞强烈向腹膜转移，类似于活病毒感染引起的转移。在这两种情况下，这种白细胞募集似乎主要通过 CK3、CK5B、CK9 和 CK10 趋化因子的产生来介导。这些结果以及 VLPs 强烈诱导非特异性淋巴细胞增殖和特异性抗 IPNV 抗体产生的事实表明，VLPs 是疫苗开发的理想候选物。
